There is an increasing need to find new molecules which can effectively modulate a wide range of biological process, especially biological processes relating to medicine and agriculture. Traditionally such molecules have been sought after using a so-called rational approach, that is the initial generation of molecules having a new structure, assaying the properties of the molecules, formulating structure-activity relationships, and then synthesising slightly amended new candidates.
Another approach involves the generation of a combinatorial library and subjecting this library to a condition in order to identify one or more compounds which are able to perform a preselected property relative to this condition. However, it remains a major problem to identity the compound having the preselected property, especially, when this compound is altered in response to the condition. As far as natural polypeptides are concerned the identity problem has been solved by connecting the encoding RNA or DNA to the polypeptide. Exemplary of this approach is phage display (Cwirla et al., Proc. Natl. Acad. Sci. USA, 87:6378-6382 (1990); Scott et al., Science, 249:386-390 (1990); and Devlin et al., Science, 249:404-406 (1990)) and mRNA-polypeptide fusion products (U.S. Pat. No. 5,843,701 and WO 00/47775).
EP 643 778 B1 discloses a method in which a polypeptide can be identified in a library of bifunctional molecules. The library comprises a plurality of bifunctional molecules produced by step-wise addition of an amino acid and a corresponding oligonucleotide to each side of a linker molecule. The library is generally produced by traditional split and combine techniques.
In an aspect of the present invention it is the object to devise an identification method using a versatile library not confined to polypeptides. In another aspect the use of a library produced by attachment of a tag to a molecular entity in a few steps is suggested, avoiding a multi-step synthesis used in the prior art.